The current grant application proposes to test the hypothesis that the major biochemical abnormality in psoriasis is a dysfunction of the cyclic AMP regulatory system in the epidermis. It was then postulated that the high mitotic rate and glycogen accumulation in this disease may be accounted for by a low cAMP level. Our preliminary data, although based on a rather limited number of cases, are summarized as follows: A microanalysis of cAMP level in frozen-dried and microdissected epidermis from psoriatic and healthy skin of the same patient shows, essentially the same values; (on a dry weight basis, the level in the psoriatic is even higher than that in the uninvolved epidermis). A response to epinephrine is, however, 10- to 20- fold stronger in the uninvolved than in the psoriatic skin. Since cAMP-phosphodiesterase appears normal in both psoriatic and uninvolved epidermis, the major biochemical lesion lies in the abnormal adenyl cyclase system of the psoriatic epidermis.